The invention pertains to a process of freeze drying of an essentially aqueous solution.
Lyophilisation (freeze drying) is a stabilising process in which the formulation is first frozen, i.e., a separation of the solvent and the solutes, and then the concentration of the solvent, mainly water, is reduced first by sublimation (primary drying) and then by desorption (secondary drying) to levels that will no longer support biological growth or chemical reaction. [Lyophilization Seminar Notes, 1993, p. 30]
Within the last decades freeze drying has become the most common method for the preparation of pharmaceuticals which are not adequately stable in solution. Among them the increasing demand for complex organic molecules, peptides and (recombinant) proteins being used as medicinal preparations have been the driving force to more scientifically investigate freeze drying cycles.
Being time consuming and expensive freeze drying is often the rate limiting process in the biopharmaceutical industries. Despite this disadvantage experience has shown that a variety of chemical reactions in aqueous solution, many of which are unacceptable in terms of product safety, are retarded in the dry state (e.g. hydrolysis, disulfide rearrangement, oxidation, aggregation etc.). Hence, freeze drying is considered one of the best methods to preserve proteins yielding products that are stable and convenient to store, ship or handle and which is accepted by the authorities as a suitable process step in the manufacture of therapeutic products.